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ABSTRACT: PURPOSE: The pathogenesis and prevention of cleft lip and palate (CL/P) have been studied mainly in clinical and animal experiments. A prophylactic poly-B-vitamin substitution during the first months of pregnancy has provided the most encouraging results for the prevention of CL/P recurrence in families at risk. In vitro studies of the palatal organ in an A/WySn mouse model have confirmed the positive influence of B-vitamins on palatal development. The present animal study was performed to analyze different B-vitamin concentrations in the serum and amniotic fluid of A/WySn mice according to the appearance of CL/P in their offspring. MATERIAL AND METHODS: Concentrations of different B-vitamins (B1, B2, B3, B5, B6, and folic acid) in serum and amniotic fluid were analyzed by high-performance liquid chromatographic detection. Immunohistochemical staining against thiamin-1 receptor was performed on histologic midface sections of A/WySn fetuses with (n = 12) and without (n = 14) CL/P. RESULTS: Vitamin B5 (P < .001) and folic acid (P < .004) concentrations in the amniotic fluid of dams with CL/P were significantly lower than in dams without CL/P. Serum concentrations of folic acid (P = .5) and B5 (P = .4) showed no difference between the 2 groups. Dams with CL/P had significantly lower thiamine concentrations in serum (P = .01) and amniotic fluid (P < .001). Histologic midface sections presented high thiamin-1 receptor expression in the palatal shelf of fetuses with CL/P. CONCLUSION: A decreased use or uptake of some B-vitamin subgroups (B1, B5, and folic acid) in amniotic fluid and serum (vitamin B1) was correlated to an increased cleft appearance in A/WySn mice. The high thiamin-1 receptor expression in the palatal tissue of mouse fetuses with CL/P may be caused by a decreased availability of vitamin B1.
Journal of oral and maxillofacial surgery: official journal of the American Association of Oral and Maxillofacial Surgeons 05/2013; · 1.58 Impact Factor
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ABSTRACT: It is well known that the hypoxia-inducible factor 1 α (HIF1α) is detectable as adaptive metabolic response to hypoxia. However, HIF1/HIF1α is detectable even under normoxic conditions, if the metabolism is altered, e.g., high proliferation index. Importantly, both hypoxic metabolism and the Warburg effect have in common a decrease of the intracellular pH value. In our interpretation, HIF1α is not directly accumulated by hypoxia, but by a process which occurs always under hypoxic conditions, a decrease of the intracellular pH value because of metabolic imbalances. We assume that HIF1α is a sensitive controller of the intracellular pH value independently of the oxygen concentration. Moreover, HIF1α has its major role in activating genes to eliminate toxic metabolic waste products (e.g., NH 3/NH 4+) generated by the tumor-specific metabolism called glutaminolysis, which occur during hypoxia, or the Warburg effect. For that reason, HIF1α appears as a potential target for tumor therapy to disturb the pH balance and to inhibit the elimination of toxic metabolic waste products in the tumor cells.
Cell cycle (Georgetown, Tex.) 09/2012; 11(21). · 5.36 Impact Factor
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ABSTRACT: PURPOSE: This study analyzed the direct influence of vitamin B-complex supplements (Polybion N, Merck Pharma GmbH, Germany) in medium on secondary palatal development in palatal organ cultures of A/WySnJ mice. Because of positive clinical experiences with prophylactic vitamin B substitution in mothers of cleft-related families, the direct influence of the vitamin B-complex on palatal tissue was analyzed. MATERIALS AND METHODS: The inbred A/WySnJ mouse strain shows a highly spontaneous, genetically determined clefting rate of 20% to 44%. One hundred seventy-seven A/WySnJ fetuses were microdissected on gestational day 14.3 before the occurrence of palatal fusion. Palatal organ cultures were prepared and incubated in chemically defined serum-free medium with different concentrations (0.1% and 1.0%) of the vitamin B-complex Polybion N for 72 hours. Palatal development was analyzed microscopically according to the 6-step visual scale that describes the approximation of palatal shelves during development. RESULTS: At the beginning of the experiment (gestational day 14.3), the palatal development of all specimens used for in vitro organ culture showed a clear approach of the palatal shelves at stage II (2.25 ± 0.78). Seventy-two hours after in vitro cultivation, the palatal shelves of the organ cultures supplemented with the vitamin B-complex showed significant growth (0.1%, P = .00017; 1.0%, P = .00078), whereas the untreated control group remained at initial developmental stage II (P = .291). CONCLUSIONS: The results of this in vitro study suggest a significant positive influence of vitamin B supplementation on palatal shelf development in organ culture. Further studies will focus on the vitamin B concentration in the amniotic fluid of dams with or without cleft in their offspring.
Journal of oral and maxillofacial surgery: official journal of the American Association of Oral and Maxillofacial Surgeons 06/2012; · 1.58 Impact Factor
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ABSTRACT: The microflora of odontogenic infections is typically polymicrobial with increased resistance rates against various antibiotics. The purpose of the present study was to analyze bacterial spectra and resistance in odontogenic infections under routineous conditions.Microbiological samples were collected and transported under routineous conditions in a prospective study of 19 patients. All Bacterial spectra and resistance rates were compared with the results of a former prospective evaluation.There were 11 men, 5 woman and 3 children (age range of 2-86 years). A total of only 38 bacterial strains were analyzed. The ratio between aerobes and anaerobes was nearly 1:1. The resistance rates were nearly the same for Penicillin G, but a 2-fold increased resistance for clindamycin against aerobes and a more than 10-fold increased resistance against anaerobes was noted.Prospective studies under standardized conditions are necessary to isolate strict anaerobes and to detect changes in antibiotic efficiency.
Wiener Medizinische Wochenschrift 06/2012; 162(13-14):316-20.
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ABSTRACT: Von 1980 bis 2005 führten wir bei 71 Frauen mit nichtsyndromalen Lippen-Kiefer-Gaumen-Spalten (LKG) oder Gaumenspalten (G) in der Familien- oder Eigenanamnese und Kinderwunsch 88-mal eine Spaltprävention mit hohen Dosen von Vitamin-B-Komplex und zusätzlich 2-mal pro Woche Actovegin® durch.Als Kontrolle dienten empirische Daten zum Wiederholungsrisiko von LKG und G. Es erfolgte die empirische Bestimmung des erwarteten Spaltrisikos ohne Vitaminprophylaxe in Abhängigkeit von der vorliegenden familiären Belastung. In 80 Fällen wurde ein gesundes Kind geboren. In zwei Fällen wurden Mikrosymptome in Form von einseitigen Lippenkerben beobachtet. Das empirisch bestimmte durchschnittliche Risiko ohne Prophylaxemaßnahmen betrug bei LKG 4,9% und bei G 2,4%. Das tatsächlich beobachtete Risiko mit Prophylaxe betrug bei LKG 2,9% (2 Mikrosymptome) und bei G 0%.Das relative Risiko als Vergleichswert zwischen erwartetem und beobachteten Risiko lag für LKG unter Einbeziehung der Mikrosymptome bei 0,6 und für G bei 0.From 1980 to 2005, 71 female patients having non-syndromic cleft lip and palate (CLP) or cleft palate (CP) themselves or in their family and desiring to have children underwent 88 times acleft prevention protocol with high doses of Vitamin B Complex and Actovegin® twice aweek. The data about the outcome of the pregnancy were prospectively collected. Empiric data of the recurrence risks from the literature depending on the cleft type were used as comparative group.In 80 cases, ahealthy child was born. In two cases microsymptoms of unilateral lip notches were observed. The observed risks with prophylaxis were 2.9% (only microsymptoms!) and 0% comparing with 4.9% and 2.4% respectively in the controls. The relative risk as reference value between expected and observed risk was 0.6 (microsymptoms) for CLP and 0 for CP.
Mund- Kiefer- und Gesichtschirurgie 04/2012; 10(5):301-305.
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ABSTRACT: To study whether coexpression of the two hypoxia-related proteins hypoxia-inducible factor (HIF)-1α and glucose transporter (GLUT)-1 has prognostic relevance in oral squamous cell carcinomas (OSCCs).
Eighty-two OSCC samples were analysed for expression levels of HIF-1α and GLUT-1 by immunohistochemistry. Protein expression was assessed with an immunoreactive score system, and the correlations between gene expression and both clinical and pathohistological parameters were examined. Overexpression of either GLUT-1 or HIF-1α was associated with poor disease-specific survival in OSCC patients. Multivariate Cox proportional-hazards regression analysis revealed that increased expression of HIF-1α was significantly associated with disease-specific survival (relative risk = 3.24, P = 0.024), as compared with the group with a low level of expression. Coexpression of HIF-1α and GLUT-1 was additively and significantly associated with adverse prognoses in patients with OSCC. Patients whose tumours had increased levels of expression of both HIF-1α and GLUT-1 were found to have a 5.13-fold increased risk of tumour-related death (P = 0.017).
Coexpression of high levels of HIF-1α and GLUT-1 is significantly correlated with prognosis in OSCC patients, suggesting that the coexpression of these proteins can be used as both an early diagnostic and independent prognostic marker.
Histopathology 03/2011; 58(7):1136-47. · 3.08 Impact Factor
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ABSTRACT: The human leucine-rich, repeat-containing G protein-coupled receptor (LGR) 5, also called GPR49, is a marker of stem cells in adult intestinal epithelium, stomach and hair follicles. LGR5/GPR49 is overexpressed in tumors of the colon, ovary and liver and in basal cell carcinomas. Moreover, an expression in skeletal muscle tissues was also detected. However, there has been no investigation regarding the expression and function of LGR5/GPR49 in soft-tissue sarcomas (STS) yet.
Seventy-seven frozen tumor samples from adult STS patients were studied using quantitative real-time TaqMan™ PCR analysis. The mRNA levels of wild type LGR5/GPR49 and a newly identified splice variant of LGR5/GPR49 lacking exon 5 (that we called GPR49Δ5) were quantified.
A low mRNA expression level of GPR49Δ5, but not wild type LGR5/GPR49, was significantly correlated with a poor prognosis for the disease-associated survival of STS patients (RR = 2.6; P = 0.026; multivariate Cox's regression hazard analysis). Furthermore, a low mRNA expression level of GPR49Δ5 was associated with a shorter recurrence-free survival (P = 0.043). However, tumor onset in patients with a lower expression level of GPR49Δ5 mRNA occurred 7.5 years later (P = 0.04) than in patients with a higher tumor level of GPR49Δ5 mRNA.
An attenuated mRNA level of the newly identified transcript variant GPR49Δ5 is a negative prognostic marker for disease-associated and recurrence-free survival in STS patients. Additionally, a lower GPR49Δ5 mRNA level is associated with a later age of tumor onset. A putative role of GPR49Δ5 expression in tumorigenesis and tumor progression of soft tissue sarcomas is suggested.
BMC Cancer 01/2011; 11:429. · 3.01 Impact Factor
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The lancet oncology 06/2010; 11(6):511-2. · 14.47 Impact Factor
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ABSTRACT: A case of cervical lymph node infiltration by a benign cellular blue nevus (CBN) and a 27-year disease history is presented. Dermal dendritic melanocytes and pigmented spindle cells presented no histological evidence of malignancy (CD34-, desmin-, PanCy-, HMB-45+, anti-S-100+, Bcl-2+, MART-1+, focally expression of melan A, 1% Ki-67+ of the tumour cell nucleoli). The differentiation of the benign blue nevus (BN) from a malignant blue nevus (MBN) and a malignant melanoma (MM) is still a challenge. Because of the malignant transformation potential of 5.2-6.3% a histological examination and a conservative surgical approach with close follow up are mandatory.
Journal of cranio-maxillo-facial surgery: official publication of the European Association for Cranio-Maxillo-Facial Surgery 03/2010; 38(8):601-4. · 1.25 Impact Factor
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ABSTRACT: Surgical treatment of cancers of the oral cavity often requires resection of the mandible, which sacrifices continuity, thereby implying considerable loss of function and aesthetics. The aim of the present study was to compare different methods of mandibular reconstruction for long-term results, complications, and factors associated with failure. During the 10-year period (1995-2005), 102 patients (73 men and 29 women, mean age 55 years, range 11-83) had a continuity resection of the mandible as described by Jewer et al. as follows: lateral continuity defect (n=53), central/lateral continuity defect (n=24), lateral/central/lateral continuity defect (n=14), central continuity defect (n=6), hemimandibular continuity defect (n=4) and central/hemimandibular continuity defect (n=1). The gap in the mandible was bridged with a titanium reconstruction plate in 73 patients, four of whom required a temporomandibular joint prosthesis. In 29 patients the mandibles were reconstructed with free autologous bone grafts fixed with miniplates. The overall 1-year success rate was 64%; 66% for the 73 patients who had miniplate/bone fixation and 63% in the 29 whose defects were bridged with a reconstruction plate. Complications were associated with the reconstruction plate in 39%. The most common complications were extraoral exposure (16%), intraoral exposure (10%), loose osteosynthesis screws (5%), fractures of the reconstruction plate (5%), and extra/intraoral exposure (1%). All fractures were noted at least 6 months postoperatively. There was no increased risk (p=0.67) depending on the osteosynthesis device used (miniplate or reconstruction plate). The risk of failure of the reconstruction plate was significantly higher in men (p=0.002) and smokers (p=0.004), whereas no increased risk was apparent for the anatomical site of the defect. Radiation reduced the 1-year success rate from 64% to 45% but not significantly so (p=0.67). There were no significant differences between the reconstruction methods. Alloplastic reconstruction devices are the treatment of choice for many patients.
British Journal of Oral and Maxillofacial Surgery 08/2009; 48(2):100-4. · 1.95 Impact Factor
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ABSTRACT: PURPOSE AND RESULTS: The aim of this prospective study was to determine the incidence of postoperative bleeding after oral surgery under local anaesthesia performed in outpatients with haemostatic disorders within a 5-year period (2003-2007). One hundred twenty one (70 males, 51 females) out of 2,056 outpatients with different haemostatic disorders (acquired or hereditary) were included in this study. The following data were recorded: medical history and general condition; medications; indication for the surgical procedure; specification of local anaesthesia; applied surgical techniques, considering the kind of haemostatic disorder; and peri- or postoperative bleeding complications. Postoperative bleeding was observed in 12 patients (9.9%). In three cases, inpatient treatment became necessary. The management of two patients with a haemostatic disorder (von Willebrand s disease and haemophilia A) is presented in short case reports. CONCLUSION: In a heterogeneous group of 121 outpatients with known haemostatic disorders, a combination of a few haemostatic agents with appropriate operative technique enables an effective wound management. In cases of failed local interventions after postoperative bleeding, further diagnostic investigations are required.
Oral and Maxillofacial Surgery 04/2009; 13(2):73-7.
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ABSTRACT: INTRODUCTION: Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant disorder with a shortened fragment of a D4Z4 repeat on chromosome 4q35. The infantile form of FSHD is relatively rare. CASE REPORT: Within this case report, we describe the orthognatic surgery in a patient with infantile FSHD to diminish the functional and esthetic disturbances in the orofacial region. We saw a 20-year-old female patient suffering from infantile FSHD with remarkable macroglossia and frontal open bite. Diagnosis was based on molecular genetic investigations. To improve the functions of the stomatognathic system, we performed a tongue reduction and a segment osteotomy in the frontal aspect of the mandible. The patient was satisfied with the functional and esthetic results. Lip competence and occlusion were significantly improved. Thus, orthognatic surgery can enhance oral function, facial esthetics, and general quality of life.
Oral and Maxillofacial Surgery 09/2008; 12(4):195-8.
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ABSTRACT: One of the operative complications during sagittal split osteotomy (SSO) in orthognatic surgery is a bad split, meaning an undesired fracture of the mandible during osteotomy. The aim of this study was to find out if there is a relation between the occurrence of bad splits during SSO and the presence of third molars, the patient's age, or the surgeon's experience. Clinical notes of 110 consecutive patients who had had a total of 220 SSOs using the Obwegeser/Dal Pont technique were evaluated and divided into three groups: 1 missing third molar (n=168); 2 retained or impacted third molar that was removed during the SSO (n=23); and 3 third molar left in place during SSO (n=29). There were a total of 12 (6%) bad splits. 9 (5%) in group 1, two (9%) in group 2, and one (3%) in group 3. There were no significant differences between groups 1-3, in particular the surgeon's qualification had no influence on the incidence. Older patients seemed more at risk of a bad split than younger ones.
British Journal of Oral and Maxillofacial Surgery 05/2008; 46(3):177-9. · 1.95 Impact Factor
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ABSTRACT: Carcinogenesis of squamous cell carcinomas in the upper aero-digestive tract (UADT) is a multi-stage process. Since 1937, micronuclei (MN) have been considered a marker for genome damage in the initiation stage. By help of the micronucleus test, carcinogenic exposure can be proven in the mucosa area of the UADT. The hypothesis to be tested was that individual oral hygiene and the dental status, respectively - just like alcohol and tobacco abuse - are associated with the micronucleus rate in cytological preparations of the buccal mucosa. In a prospective clinical observation study, we determined in 100 probands the micronucleus frequency per 1000 mucosa epithelial cells. Study participants with a high number of missing teeth (M/T index, p=0.037), a below-average papillary bleeding index (PBI, p=0.032) and periodontal status, respectively (PSI, p=0.042) possessed a higher micronucleus number in comparison with restored dental conditions. Probands with composite restorations displayed a higher MN rate (p=0.006) compared to those with amalgam. However, we could not detect any significant relation with the prosthetic status (p> or =0.075). An adjustment was made according to alcohol and tobacco. We therefore conclude that subgingival plaque and synthetic dental materials in addition to chronic alcohol and tobacco consumption might have genotoxic relevance in the oral cavity.
Oral Oncology 03/2008; 44(3):220-6. · 2.86 Impact Factor
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ABSTRACT: Squamous cell carcinomas of the upper aerodigestive tract are a global health-political challenge. Accordingly, current research efforts are aimed towards the opportunities for early recognition of risk patients, and at the recognition of risk factors related to carcinogenesis. We determined the revertant number of the variety Salmonella typhimurium TA 98 and TA 100 after incubation, with saliva samples from 100 probands as a measure of a genotoxic environment within the oral cavity, depending on the dental status as measure of oral health. Beside chronic alcohol (p=0.032) and tobacco consumption (p<0.001), the dental status displayed in partial aspects (high plaque index, high number of decayed teeth, prosthetically not rehabilitated status, p <or= 0.050) a significant connection with the genotoxic salivary activity. The periodontal status and the type of restorative filling material, as well as dental prostheses, however, had no important influence on the revertant number (p >or= 0.104). Therefore, it can be concluded that the polymicrobial supragingival plaque, as a possible independent factor, possesses a relevant mutagenic interaction with saliva, and that individual oral health is a co-factor in the development of carcinomas in the oral cavity.
Oral Oncology 10/2007; 43(9):933-9. · 2.86 Impact Factor
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ABSTRACT: The aim of the present study was to investigate radiographic and functional long-term results after condylar fractures have been reduced by an exclusively intraoral surgical approach.
A total of 25 (21 male, 4 female) consecutive patients with 30 condylar process fractures were retrospectively investigated. Clinical follow-up was performed in 19 patients (16 male, 3 female) with a total of 24 fractures. Median postoperative follow-up time was 19.7 months. Surgical indications followed specific parameters of fracture localization, dislocation, and ramus shortening. All patients were examined in accordance with the Research Diagnostic Criteria for Temporomandibular Dysfunction (RDC/TMD) and the Helkimo Index. Orthopantomograms (OPGs) were analyzed with use of the condylar morphologic scale (CMS), and mandibular ramus position and height were measured.
Fractures were classified as condylar neck (n = 2) and basis fractures (n = 28), according to criteria of the Strasbourg Osteosynthesis Research Group (SORG). Mean age of patients was 33 years (standard deviation [SD], 13 yr). RDC/TMD measurements at follow-up showed a mean mouth opening of 48 mm (SD, 9), mandibular laterotrusion right of 11 mm (SD, 3.8), laterotrusion left of 10 mm (SD, 4.5), and protrusion with a mean of 5.83 mm (SD, 3). No joint clicking, weakness of the facial nerve, or joint or muscular pain was observed. Statistical analysis of the CMS showed significantly better postoperative ramus height (P < .05).
Reduction achieved by this technique allows reconstruction of anatomic ramus height in combination with excellent functional results.
Journal of Oral and Maxillofacial Surgery 08/2007; 65(8):1470-6. · 1.64 Impact Factor
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ABSTRACT: From 1980 to 2005, 71 female patients having non-syndromic cleft lip and palate (CLP) or cleft palate (CP) themselves or in their family and desiring to have children underwent 88 times a cleft prevention protocol with high doses of Vitamin B Complex and Actovegin twice a week. The data about the outcome of the pregnancy were prospectively collected. Empiric data of the recurrence risks from the literature depending on the cleft type were used as comparative group. In 80 cases, a healthy child was born. In two cases microsymptoms of unilateral lip notches were observed. The observed risks with prophylaxis were 2.9% (only microsymptoms!) and 0% comparing with 4.9% and 2.4% respectively in the controls. The relative risk as reference value between expected and observed risk was 0.6 (microsymptoms) for CLP and 0 for CP.
Mund- Kiefer- und Gesichtschirurgie 10/2006; 10(5):301-5.
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ABSTRACT: The aim of this study was to analyse possible intra- and postoperative complications and long-term results in combined orthodontic-orthognathic treatment of mentally handicapped patients compared with a control group of patients without handicap.
A group of 20 mentally handicapped patients (male = 7, female = 13) and of 102 non-handicapped patients (male = 36, female = 66) were evaluated retrospectively. The results of the two point-discrimination sensory test and the cephalometric findings of both groups were assessed. Complications during and after the operation, the results of nerve function tests and relapse rates were reported. The statistical analysis was carried out using binary logistical regression analysis with adjustment according to the diagnosis and the type of operation (p < 0.05)
No significant differences could be found between the mentally handicapped and the non-handicapped patients. Only the nerve function test immediately postoperatively revealed differences between the two patient groups. The relapse rate in mentally handicapped patients was similar to non-handicapped patients. Forty-seven months after the operation, relapse (change in the ANB angle of more than 0.5 degrees ) was observed in four patients only (handicapped patients).
Orthognathic surgical procedures in mentally handicapped patients can be carried out with a similarly high success rate as in mentally healthy patients.
Journal of Cranio-Maxillofacial Surgery 04/2006; 34(3):156-61. · 1.64 Impact Factor
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ABSTRACT: Simultaneous radiochemotherapy (RCT) is the treatment of choice for locally advanced head and neck cancers. In order to evaluate the toxicity and the survival rates, we investigated the use of a very aggressive combination protocol that included cisplatinum and paclitaxel combined with hyperfractionated-accelerated radiotherapy. The final results of the phase II study are listed below.
For the phase II trial 32 patients (29 male, 3 female) with histologically diagnosed locally advanced non-metastatic squamous cell carcinoma of the head and neck in stage III/IV were treated from 1999 to 2003. Radiotherapy was administered as hyperfractionated-accelerated to a total dose of 70.6 Gy. The chemotherapy regime included administering cisplatinum on d 1-5 and on d 29-33 at doses of 20 mg/m(2) and during the entire course of treatment paclitaxel was administered twice a week at doses of 25 mg/m(2).
The 5-yr overall and disease-free survival rates were 48% and 43%. Twenty-two (69%) patients reached a clinically complete response and 8 (25%) a partial response (for two of the patients the response rate is not known). Two (6%) patients died during the treatment. Seven (22%) patients developed local recurrences and six of these patients have in the meantime died. With regards to the four (12%) patients who developed distant metastases, three of them have in the meantime died and two (6%) patients have died as a result of secondary malignancies. Seven out of 25 (28%) patients developed grade 3 erythema and 22 out of 31 (71%) patients developed grade 3 mucositis. No cases of grade 4 mucositis were observed; however, one patient out of 25 (4%) was classified with grade 4 dermatitis. One out of 24 (4%) patients developed grade 2 liver toxicity and 1 out of 22 patients (5%) developed grade 3 thrombopenia. Seven out of 25 patients (28%) developed a grade 3 leukopenia, and 2 out of 25 patients (8%) experienced a grade 4 eutropenic infection. Dysphagia was a significant late toxicity. Out of 24 patients, 4 (17%) developed a grade 3 dysphagia and 1 (4%) patient developed a grade 3 xerostomia. An osteoradionecrosis was seen in 2 out of 24 (8%) patients.
This very aggressive radiochemotherapy protocol yielded excellent response and overall survival rates; however it is associated with a very high rate of acute toxicity. Therefore, in such cases where acute toxicity resulted, extensive supportive care is required.
Medical Oncology 02/2006; 23(3):325-33. · 2.14 Impact Factor
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ABSTRACT: Tumor volume after the lymph node involvement is one of the most important single prognostic factor in patients of head and neck cancers treated with radiotherapy. We have recently demonstrated that the hypoxic subvolume is more important than the total tumor volume. We therefore propose the hypothesis that the presence of visible necrosis might be an important factor for cure by radiotherapy in squamous cell cancers of the head and neck.
A total of 51 patients with locally advanced inoperable (T3-4 or N2-3) squamous cell cancers of the head and neck (mean age 57 years, range 41-75 years) were prospectively investigated with regard to a possible impact of tumor volume. All patients received CT examination of the head and neck according to a standardized protocol (spiral CT, contrast enhancement after automatic injection), and the total tumor volume was calculated as the sum of volumes of all visible macroscopic tumor sites. Poorly perfused and necrotic areas (no contrast enhancement) within macroscopic tumor sites were also calculated. Patients were then treated with accelerated-hyperfractionated radiotherapy in about 6 weeks. Seventeen patients were treated with only radiation. Patients without contraindications to cisplatin chemotherapy received cisplatin chemotherapy or a combination of cisplatin and paclitaxel (N=34). The allocation of patients to certain treatment regimens was based on individual decisions in each case and not randomized.
In patients treated with radiation alone, 12/17 (71%) got recurrence whereas in patients treated with radiation plus cisplatin, only 14/34 (41%) recurred (P=0.05). The 2-year overall survival was for radiation alone versus radiation plus cisplatin 0% vs. 62% (P<0.0008). Tumors with smaller amount of necrosis (necrosis volume<4 cm3) had a good prognosis irrespective of type of treatment (radiation alone or radiation plus cisplatin). However, patients with tumors with a larger amount of necrosis (necrosis volume> or =4 cm3) had a significantly better outcome if they were treated with radiation plus cisplatin as compared to patients treated with radiation alone. In a multi-variate analysis using a Cox-regression model the type of treatment (radiotherapy plus versus without cisplatin) was the only independent prognostic factor for event-free survival (P<0.03) in the whole group.
In this non-randomized retrospective investigation with limited sample size, radiation plus cisplatin was superior to radiation alone. This resulted mainly from a higher efficacy of the radiochemotherapy regimen in patients with large and especially necrotic tumors. The prognostic and predictive impact of visible necrosis should be further evaluated.
Journal of Cancer Research and Clinical Oncology 11/2005; 131(11):758-64. · 2.56 Impact Factor
